Table 3.

Possible reasons for acquired resistance to anti-EGFR inhibitors and strategies

Factors contributing to acquired resistance to anti-EGFR inhibitors	Strategies to overcome acquired resistance to anti-EGFR inhibitors	References
Acquisition of KRAS mutations	None	66, 67
Emergence of EGFR ectodomain mutation S492R	Mutant is likely to respond to panitumumab relative to cetuximab; use panitumumab instead	68
Increased secretion of TGFα and amphiregulin in tumor microenvironment	None	77
Amplification of MET oncogene	Use MET-kinase inhibitors	74
Overexpression of IGF1 receptor	Use IGFR inhibitors	75
Amplification of HER2	Dual targeting of EGFR with lapatinib and pertuzumab or combined with neratinib and cetuximab	87
Dimerization of EGFR/HER3 and EGFR/HER2	Dual targeting of EGFR and HER3	82, 83